rs3903801

Variant names:

• chr6-24559205-A-G
• rs3903801
• NM_014809.4:c.2592-50T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014809.4(KIAA0319):​c.2592-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,588,724 control chromosomes in the GnomAD database, including 138,371 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10042 hom., cov: 32)
  • Exomes 𝑓: 0.41 (128329 hom.)
• Consequence: KIAA0319 NM_014809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.94
• Publications: 9 publications found

Genes affected

KIAA0319 (HGNC:21580): (KIAA0319) This gene encodes a transmembrane protein that contains a large extracellular domain with multiple polycystic kidney disease (PKD) domains. The encoded protein may play a role in the development of the cerebral cortex by regulating neuronal migration and cell adhesion. Single nucleotide polymorphisms in this gene are associated with dyslexia. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014809.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	NM_014809.4	MANE Select	c.2592-50T>C		intron	N/A	NP_055624.2
	KIAA0319	NM_001168375.2		c.2592-50T>C		intron	N/A	NP_001161847.1
	KIAA0319	NM_001350403.2		c.2592-50T>C		intron	N/A	NP_001337332.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIAA0319	ENST00000378214.8	TSL:1 MANE Select	c.2592-50T>C		intron	N/A	ENSP00000367459.3
	KIAA0319	ENST00000537886.5	TSL:1	c.2592-50T>C		intron	N/A	ENSP00000439700.1
	KIAA0319	ENST00000616673.4	TSL:1	c.825-50T>C		intron	N/A	ENSP00000483665.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49788 AN: 151976 Hom.: 10051 Cov.: 32

Gnomad AFR AF: 0.0961

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.339

GnomAD2 exomes AF: 0.369 AC: 87483 AN: 236832 AF XY: 0.383

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.233

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.220

Gnomad FIN exome AF: 0.418

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.420

GnomAD4 exome AF: 0.414 AC: 595218 AN: 1436630 Hom.: 128329 Cov.: 28 AF XY: 0.415 AC XY: 295901 AN XY: 712752

African (AFR) AF: 0.0792 AC: 2598 AN: 32804

American (AMR) AF: 0.245 AC: 10410 AN: 42566

Ashkenazi Jewish (ASJ) AF: 0.528 AC: 13255 AN: 25094

East Asian (EAS) AF: 0.208 AC: 8208 AN: 39428

South Asian (SAS) AF: 0.336 AC: 28016 AN: 83394

European-Finnish (FIN) AF: 0.419 AC: 21948 AN: 52400

Middle Eastern (MID) AF: 0.434 AC: 1766 AN: 4072

European-Non Finnish (NFE) AF: 0.442 AC: 485584 AN: 1097622

Other (OTH) AF: 0.395 AC: 23433 AN: 59250

GnomAD4 genome AF: 0.327 AC: 49762 AN: 152094 Hom.: 10042 Cov.: 32 AF XY: 0.326 AC XY: 24251 AN XY: 74328

African (AFR) AF: 0.0957 AC: 3975 AN: 41536

American (AMR) AF: 0.316 AC: 4827 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1828 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1078 AN: 5180

South Asian (SAS) AF: 0.330 AC: 1588 AN: 4816

European-Finnish (FIN) AF: 0.422 AC: 4454 AN: 10560

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30874 AN: 67948

Other (OTH) AF: 0.338 AC: 714 AN: 2110

Alfa AF: 0.419 Hom.: 24500

Bravo AF: 0.309

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.020
DANN	Benign	0.21
PhyloP100		-3.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3903801; hg19: chr6-24559433; COSMIC: COSV65497781;